Botanicals and Menopause – No Effect
Black Cohosh is a common herbal or botanical treatment for the hot flashes and other symptoms of menopause. This treatment appeals to women who want a more natural or gentle approach to their symptoms. Unfortunately, as the latest research shows, it doesn’t work.
Interest in herbal medicine has increased in the last 15 years as a response to weakened regulation and a successful marketing strategy by the supplement industry in the context of a cultural phenomenon of changing attitudes toward medicine. This has mainly led to, however, confusion about what herbal therapy really is. Most people I talk to think of herbal treatments as natural supplements – but they are not supplements and being “natural” is irrelevant. In fact it is much more accurate to think of them as unpurified drugs.
Botanical research is a legitimate and useful branch of pharmacology, with its own experts. The plant kingdom is a vast chemistry laboratory, specializing in chemicals that have some effect on other living things. The process of experimentation through evolution is slow, but has had hundreds of millions of years to operate. As a result we are surrounded by plant-based chemicals – some benign, most toxic, and a few with pharmacological properties we can exploit to our advantage if we’re careful.
That these chemicals are “natural” is meaningless. Beyond the fact that the term in this context has no useful operational definition, that these chemicals exist in nature should give us no comfort. They exist for the survival of the plant, mostly at the expense of animals who might want to eat it. No plant evolved to be a useful medicinal for one egocentric mammalian species. Toxicity, however, is all about dose, and in essence all useful drugs are simply toxins with a dose range in which they have an effect that can be exploited with acceptable side effects.
Also, plants have dozens or hundred of chemicals in them, and these vary in different parts of the plant, in different times of the season, in different regions, and from year to year. They are very dirty drugs, with variable doses of potentially useful but also strictly harmful substances. Botanical pharmacology focuses on identifying useful plants, and then figuring out which chemical substances in them are useful and which are simply adding toxicity. Useful chemicals can then be purified, quantified, and studied for their biochemistry and net health effects.
I still have a hard time understanding why someone would want to treat themselves with a dirty herb containing highly variable doses of multiple chemicals, rather than a precisely known quantity of a specific chemical with known properties. The justification I am almost always given is because they are “natural” – but as I pointed out, this is no justification at all, but clever marketing bordering on mythology.
The one saving grace of herbs is that the doses of most chemicals within them is likely to be low and therefore below the level of toxicity – or any useful effect, either. This does not mean their safety can be assumed, and many herbal remedies have been found to have toxicity, (like kava kava and liver toxicity or kidney failure from a variety of botanicals) or to interfere with prescription drugs (so-called drug-drug interactions – because they’re drugs).
Once modern pharmacology came into its own our accumulated wealth of botanical knowledge was raided for useful drugs, and they now comprise the majority of the drugs we use today. We have already plucked the low hanging fruit. There are likely to still be useful drugs out there in the plant kingdom, but it will take some investigation and research to find them. Such efforts are ongoing, and will likely continue to feed pharmacy shelves for years to come.
However, the herbal remedies that have come into popular use are generally not the result of investigation and careful research, but either tradition (read anecdotes) or modern marketing masquerading as tradition. For example, echinacea may have been used by Native Americans for many things (as was tobbaco, incidentally) but they did not use it for the common cold. That use was an invention of a German herbalist who used the Native American angle for marketing purposes.
It is therefore not a surprise that the herbs most commonly marketed today for common ailments (read large customer base) have mostly failed in clinical trials. Gingko does not work for memory or mental focus, echinacea does not treat the common cold or its symptoms, and St. John’s Wort has minimal to no effect on depression. Black cohosh for menopausal symptoms was held up as an herbal remedy that actually works, but now we have evidence from a double-blind trial that is clearly negative.
This trial had four arms - including black cohosh, red clover, placebo, and standard hormonal therapy. They followed women with menopausal symptoms for 12 months and found that, over time, they all had a decrease in symptoms by 34, 57, 63 and 94 percent respectively. The black cohosh and red clover were not statistically significantly different from placebo, while the hormonal therapy was significantly improved from placebo. The primary weakness of the study, which was generally well designed, was that it enrolled only 89 women – this is enough to run meaningful statistics, but is smallish for a clinical study of this type.
The study also examined memory in the subjects and found no difference again among black cohosh, red clover, and placebo and a slight negative effect from hormonal therapy. So – standard hormonal therapy works, with a slight side effect on memory. The botanicals black cohosh and red clover had no detectable effects or side effects – not surprising. No one study is ever the final word on questions of clinical safety and efficacy – but the trend for research into popularly marketed herbs is definitely negative.
This, of course, raises many questions about regulation and research. The current regulation in the US is abysmal – botanical drugs are treated as if they were vitamins, and companies can even make pseudo-health claims for them (so-called structure-function claims), while having no obligation to prove safety. Research is now often funded by the NCCAM, which recently came under criticism for spending 2.5 billion dollars of tax payer money over the last decade and having nothing to show for it. This might have something to do with using politics to create a center specifically to bypass the usual methods of deciding what is useful to research.
As I said – botanical research is already a separate and useful branch of pharmacology that can be funded through other centers at the NIH. In fact this legitimate research is marginalized when brought under the umbrella of “alternative medicine” – another marketing term with no useful definition.
The good news is that quality clinical research into the effectiveness and safety of commonly used herbal remedies is being done. This research recently has largely been negative, which is not surprising given the history and nature of many of the products being studied. The bad news is that common use, regulation, and marketing are almost completely divorced from the scientific research.What, then, one might wonder, is the purpose of the research?
The woo market should pay for chemical analyses and animal tests to show that what they market is at least harmless – better still if they’re made to prove efficacy. Enough of the weasel-wording on many of these products; the manufacturers and retailers should be honest.
I thought about drug hunting in plants 20 years ago, but even then I realized that I could spend many years and get no useful results. I opted for instant gratification instead and got into developing instrumentation. Back when I was considering it, I had a short list of plants I could look at which may have had desirable properties. Even my short list didn’t really have anything of great interest to me; the maladies they were alleged to treat were already very effectively treated by existing drugs. On the other side of things, even 15 years ago many chemists opted for identifying receptors and targeting drug synthesis rather than playing with plants.
I would love to see the fight to get them to do animal studies. They wouldn’t want to harm any little bunnies by testing their products!
I seem to remember Simon Singh on the SGU saying that St. John’s Wort actually does work for depression, though of course it has the usual issues of dosage control found in herbs.
Just looked it up, it was on SGU #144 (a gross episode if ever there were one) on April 23rd 2008. Is there new information since then or was he wrong or was he overstating its efficacy?
I feel somewhat conflicted about herbal remedies. If an herb has real medicinal value and is taken under the supervision of a doctor, and the cost is significantly lower than a conventional drug, then I feel like dosage control is a weak objection.
I know its not feasible now, but wouldn’t it be acceptable to have them regulated for safety and efficacy and then incorporated into the medical system for low income families or cheaper insurance plans?
No plant evolved to be a useful food or spice for one egocentric mammalian species. Therefore, we should stop eating plants.
Max – nice false argument ad absurdum – a field of straw men. I never said we should not use plant-based pharmaceuticals. We can and have found lots of useful medicinal plants. We have also found lots of food we can eat, but there is much more out there that is toxic. We have also cultivated plants to eat – they did not evolve to be what we eat today – we made them that way.
But, using plants for medicine is much trickier than for nutrition. You have to regulate the dose and bioavailability and understand the nature of disease and drug-drug interactions, half-lives, etc.
Drew – There probably is a small effect on depression from St. John’s Wort – which is why I wrote “minimal to no effect” and not just “no effect.” There is no efficacy for major depression. There is mild efficacy for minor depression – but the effects are not impressive to the point that they are not convincing.
There is, however, an MAO inhibitor in St. John’s Wort which is probably the active ingredient of any real anti-depressant effect. This is a drug – and a tricky drug to use, with lots of incompatibilities. The herb also is known to interfere with HAART drugs for HIV. And, studies of potential active ingredients in St. John’s Wort found a 17 fold difference in dose from pill to pill. That is huge, and incompatible with rational pharmacotherapy, in my opinion.
In short St. John’s Wort is the poster child for everything suboptimal about popular herbal remedies – they are drugs with low but highly variable doses, with multiple potential active ingredients, and loads of potentially very serious drug-drug interactions, and only very weak and unconvincing effects in clinical trials.
“No plant evolved to be a useful food or spice for one egocentric mammalian species. Therefore, we should stop eating plants.”
Plants evolved many and various compounds to make them more or less delicious to various herbivorous species. Some of those things we also find delicious. Most of them we do not, and we breed them out the best we can. (Go have yourself some wild almonds if you don’t believe me.)
No plant evolved medicines for any other species. Those are side effects of usually toxic compounds meant to dissuade predators or competitors. Production of these compounds depends on season, climate, locale, and interactions between the plant, its competitors and of course its predators. (Think of how the same wine differs from place to place.) That’s why it ends up taking so much effort to figure out what good a plant can be, medicine-wise.
Ever watch Survivorman? He’s in a lush jungle, yet he can barely find food, because almost everything is inedible or poisonous. Yet monkeys and natives figured out what’s edible. Not only that, they figured out which herbs are antidotes to certain poisons. That’s pretty incredible, but no more incredible than products of evolution. It’s amazing what natural selection can do, given enough time.
Do all the skeptics agree that medical marijuana is a dirty herb containing highly variable doses of multiple chemicals, compared to synthesized THC?
I can’t speak for all skeptics – but in my opinion it is certainly a dirty drug, and not a very safe drug delivery system.
http://www.webmd.com/cancer/news/20090623/marijuana-smoke-linked-to-cancer
@Steven Novella
Don’t forget that St John’s Wort also contains a potent CYP3A4 inducer, and a CYP1A1, CYP1B1, and CYP2D6 inhibitor, causing a rash of clinically significant drug-drug interactions. Even if St John’s Wort does have a small effect on depression, its effect on other medications makes it unacceptably unsafe to use.
@Max
Agreed, smoking the plant isn’t the safest way of doing it. THC and Cannabidiol both appear to have useful clinical applications (and possibly in a combined therapy too) so more needs to be done to allow access to synthesized quantities of the drugs.
I’ve recently started a blog, the information you provide on this site has helped me tremendously. Thank you for all of your time & work.
Speaking of St. John’s Wort: It is in deed used widely here in Germany, and even prescribed. Because of its liver toxicity, higher dosed pills are no longer available without a prescription, however; the indication had to be changed to “mild depression”, not “medium” any more. (And of course the woo community lamented greatly over this).
My personal experience: About 5 years ago, I asked my family doctor to prescribe me something for depression quickly (it’s not easy getting an appointment with a psychiatrist). She prescribed St. John’s Wort pills. (Some family doctors love to prescribe herbal stuff, and I live in a very CAM-infested area).
Effect on my depression: Zero. All I got was a permanent dark-pigmented spot in my face, due to the heightened light sensitivity caused by my “natural” pills. (Later, my doctor prescribed Citalopram, which was very helful, and with hardly any side effects. I didn’t get addicted, either.)
Last year I only *touched* a plant of St. John’s Wort when I saw it in a garden center. I rubbed a leaf between two fingers, just to see what it smells like. It was a very sunny day. The next day, half my forehead had become several shades darker than the rest of me – permanently. (Avoiding the sun makes it less visible, at least, so thanks to St. John’s natural wort, I’ve become a pale-skinned SPF 50 junkie).
What an annoying side effect! Natural, Shmatural. I used to make fun the cult of “natural” by reminding people that hemlock was all natural and still deadly. Unfortunately, it seems hardly anybody knows what hemlock is these days.